NCT04083235 · CITED IN SOURCE DOCUMENTS

A Study to Assess the Effectiveness and Safety of Irinotecan Liposome Injection, 5-fluorouracil/Leucovorin Plus Oxaliplatin in Patients Not Previously Treated for Metastatic Pancreatic Cancer, Compared to Nab-paclitaxel+Gemcitabine Treatment

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2026-04-20

The purpose of this study is to look at the efficacy and safety of Irinotecan liposome injection in combination with other approved drugs used for cancer therapy, namely 5 fluorouracil/leucovorin (5FU/LV) plus oxaliplatin compared to nab-paclitaxel + gemcitabine treatment in improving the overall survival of patients not previously treated for metastatic pancreatic cancer.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Progression Free Survival (PFS)

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outcome · POSTED

Overall Response Rate (ORR)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Histological or cytologically confirmed adenocarcinoma of the pancreas that has not been previously treated in the metastatic setting. * Initial diagnosis of metastatic disease must have occurred ≤6 weeks prior to screening. * Subject has one or more metastatic lesions measurable by computed tomography (CT) scan (or magnetic resonance imaging (MRI), if the subject is allergic to CT contrast media) according to RECIST Version 1.1 criteria. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Subject has adequate biological parameters as demonstrated by the following blood counts:(a) Absolute neutrophil count (ANC) ≥2000/mm3 without the use of hemopoietic growth factors within the last 7 days prior to randomisation (b) Platelet count ≥100,000/mm3 (c) Haemoglobin (Hgb) ≥9 g/dL obtained ≤14 days prior to randomisation. * Adequate hepatic function as evidenced by: (a) Serum total bilirubin ≤1.5x ULN (biliary drainage is allowed for biliary obstruction), and (b) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x upper limit of normal (ULN) (≤5x ULN is acceptable if liver metastases are present). * Adequate renal function as evidenced by creatinine clearance ≥30 mL/min. * Adequate coagulation studies (obtained ≤14 days prior to randomisation) as demonstrated by prothrombin time and partial thromboplastin time within normal limits (≤1.5xULN ). Exclusion Criteria: * Prior treatment of pancreatic cancer in the metastatic setting with surgery, radiotherapy, chemotherapy or investigational therapy * Prior treatment of pancreatic adenocarcinoma with chemotherapy in the adjuvant setting, except those where at least 12 months have elapsed since completion of the last dose and no persistent treatment-related toxicities are present. * Subject has only localised advanced disease. * Documented serum albumin \<3 g/dL * Known history of central nervous system (CNS) metastases. * Clinically significant gastrointestinal disorder * History of any second malignancy in the last 2 years * Concurrent illnesses that would be a relative contraindication to trial participation * Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1 * Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma * Known low or absent dihydropyrimidine dehydrogenase (DPD) activity
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Irinotecan liposome injection, oxaliplatin, 5 FU/LV, will be administered on Days 1 and 15 of each 28-day cycle (until progression or unacceptable toxicity).
intervention Names
Drug: Irinotecan Liposomal Injection
Drug: Oxaliplatin
Drug: 5Fluorouracil
Drug: Leucovorin
label
Irinotecan liposome injection + Oxaliplatin + 5-FU/LV
type
EXPERIMENTAL
description
Nab-paclitaxel and gemcitabine will be administered on Days 1, 8 and 15 of each 28-day cycle (until progression or unacceptable toxicity).
intervention Names
Drug: Nab-paclitaxel
Drug: Gemcitabine
label
Nab-paclitaxel + Gemcitabine
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Irinotecan liposome injection + Oxaliplatin + 5-FU/LV
description
Irinotecan liposome injection is irinotecan in the form of the sucrosofate salt, encapsulated in liposomes for i.v. infusion. It is supplied in sterile, single-use vials containing 10 mL of irinotecan liposome injection at a concentration of 4.3 mg/mL free base equivalent (FBE).
name
Irinotecan Liposomal Injection
other Names
Onivyde®
Nal-IRI
type
DRUG
arm Group Labels
Irinotecan liposome injection + Oxaliplatin + 5-FU/LV
description
Oxaliplatin injection, USP is supplied in single-dose vials containing 50 mg, 100 mg or 200 mg of oxaliplatin as a sterile, preservative-free, aqueous solution at a concentration of 5 mg/mL.
name
Oxaliplatin
other Names
Eloxatin®
type
DRUG
arm Group Labels
Irinotecan liposome injection + Oxaliplatin + 5-FU/LV
description
Fluorouracil injection, USP is a colorless to faint yellow, aqueous, sterile, nonpyrogenic injectable solution available in 50 mL and 100 mL pharmacy bulk package. Each mL contains 50 mg fluorouracil in water for injection, USP.
name
5Fluorouracil
other Names
Adrucil®
flurouracil
5-FU
type
DRUG
arm Group Labels
Irinotecan liposome injection + Oxaliplatin + 5-FU/LV
description
Leucovorin Calcium for Injection is supplied in vials ranging from 50-500 mg and available as an injectable solution or lyophilized powder for reconstitution.
name
Leucovorin
other Names
Folinic Acid
type
DRUG
arm Group Labels
Nab-paclitaxel + Gemcitabine
description
Nab-paclitaxel is a lyophilised powder containing 100 or 250 mg of paclitaxel formulated as albumin-bound particles in single-use vials for re-constitution. Each mL of the reconstituted formulation will contain 5 mg/mL paclitaxel.
name
Nab-paclitaxel
other Names
Abraxane®
type
DRUG
arm Group Labels
Nab-paclitaxel + Gemcitabine
description
Gemcitabine for injection is a lyophilised powder for solution for infusion, with each single use vial containing 200 mg, 1 g or 2 g of gemcitabine.
name
Gemcitabine
other Names
Gemzar®
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 770
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
The OS was defined as time from the date of randomization to the date of death due to any cause. Participants who did not have a date of death recorded at the time of the final analysis were censored at the last known time that the participant was alive. The median OS was measured using Kaplan-Meier technique.
measure
Overall Survival (OS)
time Frame
Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, end of treatment (EoT) visit, then every 2 months thereafter up to primary completion date (PCD) of 23 July 2022 (maximum of 893 days)

secondary Outcomes

description
PFS was defined as the time from the date of randomization to the first documented disease progression using response evaluation criteria in solid tumors (RECIST) Version 1.1 as per Investigator assessment or death due to any cause. The median PFS was measured using Kaplan-Meier technique.
measure
Progression Free Survival (PFS)
time Frame
Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose up to PCD of 23 July 2022 (maximum of 893 days)
description
The ORR was defined as the percentage of participants with a best overall response (BOR) characterized as either a complete response (CR) or partial response (PR) per RECIST Version 1.1. BOR was defined as the best response as recorded from randomization until documented objective disease progression using RECIST Version 1.1. As per RECIST version 1.1, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. The ORR was calculated using Clopper-Pearson method.
measure
Overall Response Rate (ORR)
time Frame
Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose up to PCD of 23 July 2022, (maximum of 893 days)

Full study description

brief Summary: The purpose of this study is to look at the efficacy and safety of Irinotecan liposome injection in combination with other approved drugs used for cancer therapy, namely 5 fluorouracil/leucovorin (5FU/LV) plus oxaliplatin compared to nab-paclitaxel + gemcitabine treatment in improving the overall survival of patients not previously treated for metastatic pancreatic cancer.

Source references

references

citation
Abdelrahim M, Khan G, Hatoum H, Zervoudakis A, Dayyani F, Zhang L, Li J, Maxwell F, O'Reilly EM, Wainberg ZA, Bullock A. Impact of UGT1A1*28 polymorphism in patients with metastatic pancreatic ductal adenocarcinoma treated with NALIRIFOX in the NAPOLI 3 trial. Future Oncol. 2026 May;22(12):1421-1428. doi: 10.1080/14796694.2026.2664776. Epub 2026 May 4.
pmid
42080361
type
DERIVED
citation
Wainberg ZA, Melisi D, Macarulla T, Pazo Cid R, Chandana SR, De La Fouchardiere C, Dean A, Kiss I, Lee WJ, Goetze TO, Van Cutsem E, Paulson AS, Bekaii-Saab T, Pant S, Hubner RA, Xiao Z, Chen H, Benzaghou F, O'Reilly EM. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet. 2023 Oct 7;402(10409):1272-1281. doi: 10.1016/S0140-6736(23)01366-1. Epub 2023 Sep 11.
pmid
37708904
type
DERIVED